DESCRIPTION: Epidemiologic studies indicate that exposure to electromagnetic fields in the environment increases the risk for disease, particularly cancer. Pre-transcriptional models have been proposed to explain the observations. In this view, EMF-related carcinogenesis occurs as a consequence of field-induced changes in membrane-bound glycoproteins, leading to changes in intercellular second-messenger systems and gene expression in the affected cell. The hypothesis underlying the work proposed here is that EMF effects are post- translational with respect to the EMF-detecting cell: fields are detected by a neural electrogenic, membrane-bound protein, and the resulting subthreshold changes in membrane potential modify ongoing oscillatory behavior thereby constituting an afferent signal to the thalamus. The resulting efferent signals mediate a nonspecific adaptive response to the EMF; chronic activation of the adaptive system adversely affects immuno-surveillance by natural killer cells, thereby making the occurrence of clinical disease more likely than would have been the case in the absence of EMF exposure. The prediction of immunosuppression in chronically exposed animals will be tested in the proposed work by exposing mice to EMFs, and measuring the effect on the phenotype of the lymphoid cells. Separate groups of male and female mice will be exposed to 5, 50, 500 mG and 5G, 60 Hz for periods ranging from one day to 25 weeks, and the number of NK cells, T cells, and B cells in the spleen, blood, lymph nodes, and bone marrow will be determined as a function of intensity and duration of field exposure, and compared with values measured in sham-exposed animals. 51Cr-release assays will be used to measure the effect of field exposure on the lytic function of constitutive and inducible (with polyinosinic:polycytidyllic) NK cells, and cytotoxic T lymphocytes generated in mixed lymphocyte cultures from the spleen. In addition, an in vitro assay involving IL-2 activation of splenic NK cells to lyse tumor targets will be used to characterize the inducibility of lymphocytes from exposed animals.